Pharmacological characterization of D-aminophosphonovaleric acid antagonism of amino acid and synaptically evoked excitations on frog motoneurones in vitro: an intracellular study

Abstract

The effect of D-aminophosphonovaleric acid (D-APV) on the depolarizations induced by N-methyl-D-aspartate (NMDA), glutamate, aspartate or quisqualate was studied with intracellular recordings from frog motoneurones in vitro. D-APV (0.5-10 microM) produced a slight hyperpolarization of the motoneuronal membrane without significant changes in input conductance. In control and tetrodotoxin-containing solutions the depolarizations induced by NMDA were strongly reduced by D-APV while quisqualate depolarizations were unaffected. Responses to glutamate and aspartate were antagonized to an intermediate level. The relatively small conductance increases evoked by excitatory amino acids were unaltered in solutions containing D-APV. The amplitude of monosynaptic excitatory postsynaptic potentials (e.p.s.ps) was strongly depressed by D-APV. The amplitude of polysynaptic e.p.s.ps was little changed but their decay time was reduced. It is suggested that D-APV is a powerful and selective NMDA receptor antagonist and that an endogenous amino acid acting via NMDA receptors may be the transmitter of monosynaptic e.p.s.ps on frog motoneurones.